Dagum Paul, Giovangrandi Laurent, Levendovszky Swati Rane, Winebaum Jake J, Singh Tarandeep, Cho Yeilim, Kaplan Robert M, Jaffee Michael S, Lim Miranda M, Vandeweerd Carla, Iliff Jeffrey J
Applied Cognition Inc., Redwood City, CA, USA.
Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
Nat Biomed Eng. 2025 May 27. doi: 10.1038/s41551-025-01394-9.
Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimer's and Parkinson's disease. The measurement of glymphatic function in the human brain has been elusive due to invasive, bespoke and poorly time-resolved existing technologies. Here we describe a non-invasive multimodal device for the continuous measurement of sleep-active changes in parenchymal resistance in humans using repeated electrical impedance spectroscopy measurements in two separate clinical validation studies. Device measurements successfully paralleled sleep-associated changes in extracellular volume that regulate glymphatic function and predicted glymphatic solute exchange measured by contrast-enhanced MRI. We replicate preclinical findings showing that glymphatic function is increased with increasing sleep electroencephalogram (EEG) delta power and is decreased with increasing sleep EEG beta power and heart rate. The present investigational device permits the continuous and time-resolved assessment of parenchymal resistance in naturalistic settings necessary to determine the contribution of glymphatic impairment to risk and progression of Alzheimer's disease and to enable target-engagement studies that modulate glymphatic function in humans.
动物模型中的类淋巴功能有助于清除大脑中的蛋白质，这些蛋白质的错误聚集与包括阿尔茨海默病和帕金森病在内的神经退行性疾病有关。由于现有技术具有侵入性、定制性且时间分辨性差，人类大脑中类淋巴功能的测量一直难以实现。在此，我们描述了一种非侵入性多模态设备，该设备通过在两项独立的临床验证研究中重复进行电阻抗光谱测量，连续测量人类实质阻力的睡眠相关变化。设备测量结果成功地与调节类淋巴功能的细胞外体积的睡眠相关变化平行，并预测了通过对比增强MRI测量的类淋巴溶质交换。我们重复了临床前的研究结果，即类淋巴功能随着睡眠脑电图（EEG）δ波功率的增加而增强，随着睡眠EEGβ波功率和心率的增加而减弱。目前的研究设备允许在自然环境中对实质阻力进行连续和时间分辨的评估，这对于确定类淋巴损伤对阿尔茨海默病风险和进展的影响以及开展调节人类类淋巴功能的靶点参与研究是必要的。
